Special Feature

Heliox in Acute Severe Asthma

By David J. Pierson, MD

Alvan Barach, who pioneered the clinical use of oxygen, was also the first investigator to treat acute asthma by having the patient breathe a mixture of helium and oxygen. In 4 adult asthmatics, Barach demonstrated a reduction in dyspnea after just a few breaths of the helium-oxygen mixture, now known as heliox.1 This therapy received little subsequent attention until the 1980s, but in the last decade there has been a resurgence of both publications and clinical use of heliox in acute severe asthma.2 Although I know of no national data, my impression is that it is currently much more widely used, especially in emergency departments, than at any time in the past. In addition to its use via mask in nonintubated patients with acute asthma, there are also a number of reports of the administration of heliox during mechanical ventilation in both status asthmaticus and severe chronic obstructive pulmonary disease. In this brief review I summarize the arguments in favor of using heliox in asthma, discuss the findings of several recent comprehensive literature reviews, and offer my personal opinion on how heliox fits in with the other available therapies for acute severe asthma.

What is Heliox and What Does it Do?

Helium is an inert, colorless, odorless gas occurring naturally in the atmosphere. Other than hydrogen, it is the least dense gas known, which accounts for its use in weather balloons and blimps. Its medical interest also arises from its low density. Pure helium is only one-seventh as dense as nitrogen but slightly more viscous. The addition of 20% oxygen increases the density to one-third that of air, and it is doubtful whether mixtures much more than 30% oxygen are appreciably different from their nitrogen counterparts. Heliox is most commonly used in mixtures of 80:20 or 70:30 helium:oxygen and is available in large compressed-gas cylinders (H tanks). The physical properties of heliox decrease the tendency for gas turbulence in obstructed airways, tending to make flow more laminar and hence more energy-efficient.

Table

Potential Benefits of Heliox Administration in Acute Severe Asthma

Benefit  Mechanism Potential Implications
Decreased resistive work of breathing Reduced turbulent flow and increased laminar flow in airways Increased peak expiratory flow; Decreased pulsus paradoxus; Decreased ventilatory muscle; fatigue
Avoidance of need for mechanical ventilation; 
Reduced dynamic hyperinflation More complete exhalation (to lower lung volume) Decreased work of breathing; Decreased dyspnea
Improved airway distribution of aerosols Increased laminar flow; Increased peripheral deposition of particles Increased effectiveness of bronchodilators

Why Might Heliox be Beneficial in Acute Severe Asthma?

As shown in the Table, there are several theoretical reasons why breathing heliox might be physiologically advantageous for a patient with acute severe asthma in comparison to breathing a mixture of nitrogen and air. Most important is probably the effect on resistance in the airways. With more laminar flow, less resistive work is required to move air in and out of the lungs, and the pressures that must be generated to do so are decreased. As a result, peak inspiratory and expiratory flows are increased, and less ventilatory muscle work is required for a given minute ventilation. Heliox has also been demonstrated to reduce pulsus paradoxus in acute asthma. All these effects would tend to relieve fatigue and respiratory distress and could theoretically reduce the need for mechanical ventilation.

Increased airway resistance promotes air trapping and dynamic hyperinflation in acute asthma, and heliox should have a beneficial effect on these as well, with an attendant reduction in work of breathing and relief of dyspnea. Studies have also shown that the deposition of aerosols in the airway is augmented by the presence of helium in the breathing mixture.3 This in turn could lead to greater bronchodilator effect and more rapid improvement in airway function in acute severe asthma.

What Do Heliox’s Advocates Say?

There are thus a number of sound theoretical reasons why breathing heliox should be beneficial not only in acute asthma but also in COPD as well as epiglottitis, croup, and other forms of upper airway obstruction. Early case series suggested that fewer patients presenting to the emergency department (ED) with acute severe asthma required hospitalization, and that intubation could perhaps be avoided, with heliox delivered by mask. There were also reports of dramatic improvement in airway pressures and arterial blood gases in intubated, ventilated patients. As a result, heliox has become a standard component of therapy in some EDs, and many clinicians advocate its use when initial management with bronchodilators and corticosteroids does not result in prompt improvement.

What Does the Evidence Say?

Heliox can indeed improve bronchodilator delivery in acute asthma. Recently, a randomized, controlled trial of albuterol nebulization via heliox vs oxygen in 45 patients presenting to the ED with acute asthma4 showed more effective drug administration with the former. The patients were given 3 nebulizer treatments using the same amount of drug. That more drug reached the lower respiratory tract with heliox was shown by the findings of significantly greater improvement in spirometry (32% vs 15% improvement in forced expiratory volume in the first second [FEV1] after the first nebulizer treatment) and significantly higher heart rates.

The study just mentioned did not address the effect of heliox on patient outcomes, and here the literature is much less impressive. A Cochrane Review of literature published through September 20015 found 4 randomized controlled trials that met Rodrigo and associates’ a priori inclusion criteria, 3 studies involving adults, and a fourth including only children, with a total of 288 patients. The main outcome in all 4 trials was 1 or more measures of pulmonary function (mainly peak expiratory flow [PEF]), and systematic review of the pooled data revealed no significant differences. Comparisons of data from adults vs children, high vs low heliox dose, and high vs low study design quality, revealed no differences. The reviewers concluded that the existing evidence did not provide support for heliox administration to patients presenting to the ED with moderate-to-severe acute asthma.5

Chest recently published 2 systematic reviews of heliox therapy in acute asthma.6,7 These reviews and their accompanying editorials8,9 illustrate how the message from the same basic data can be spun differently by different authors.

Rodrigo et al6 reviewed both randomized and nonrandomized prospective controlled trials comparing heliox to placebo, with results including pulmonary function tests and other physiologic measures, adverse effects, hospital admissions, and clinical outcomes. They included 7 trials with a total of 392 patients. Either PEF or FEV1 was the primary outcome variable in 6 studies; 2 studies measured airway resistance. Pooling the data from all studies, there were no differences in these outcomes with heliox vs placebo. Data from those studies that used heliox to deliver nebulized therapy (including the study by Kress et al summarized above4), found a nonsignificant overall increase in pulmonary function (standardized mean difference -0.21; 95% confidence interval, -0.43 to 0.01), and no difference in the rate of hospital admission. Two of these latter studies that used heliox-driven nebulization found significant increases in heart rate, but no clinically important side effects were reported. Rodrigo et al concluded that, although the existing studies are small and suffer from various design weaknesses, available evidence does not support the administration of heliox to ED patients with moderate-to-severe asthma.

In an editorial accompanying the Rodrigo review, Manthous8 points out that no study to date has examined the really important issue of whether heliox improves outcomes in patients with acute severe asthma who do not respond satisfactorily to other therapies in the ED. He cautions that heliox should not be used routinely, but that it would be reasonable to try it in patients with severe, refractory status asthmaticus—if used carefully, as he and others have described.2 Manthous also mentions that, in his last 10 years of practice, he has not encountered a case of severe asthma that did not respond to aggressive management (without heliox).

In a different take on the same basic data set and in the same issue of Chest, Ho and associates7 reported an extensive statistical examination of pooled data from 4 of the 7 studies (278 patients) reviewed by Rodrigo et al. Using data from these 4 studies, Ho et al performed meta-analyses on PEF as a percent of the predicted value, saturation as measured by pulse oximetry, and dyspnea index. "These meta-analyses demonstrated an advantage with the use of heliox when compared with airO2 at the 92% [sic] confidence level for PEF."7 The weighted mean difference to which Ho et al refer was +3%, with a 95% confidence interval of -2% to +8%. Similarly, they describe a "slight improvement" in dyspnea index with heliox vs air-oxygen, with a 95% confidence interval of 0.04 to 1.16. No differences were claimed for pulse oximetry. Ho et al conclude that heliox may offer "mild-to-moderate benefits" in patients with acute asthma within the first hour of use, but less apparent benefit subsequently. Ho et al cite air entrainment around the mask (and thus dilution of the helium) as a methodologic flaw in the studies that did not show heliox to be superior to air-oxygen mixtures, and also discuss other possible reasons why other reviews have not found statistically significant benefits from heliox therapy.

Kass, in an editorial accompanying the Ho et al review9, describes 2 patients with severe acute asthma who improved dramatically on heliox, but cautions that patients should be carefully selected for treatment with this agent. He points out that, since heliox is not therapeutic in itself but only a bridge until the primary agents exert their effect, ". . . it is unlikely that it will reduce hospital admissions, hospital or ICU length of stay, or hospital mortality. It will provide rapid and marked relief of dyspnea to many patients without any detrimental effects. Since its therapeutic index is so high and its onset and offset of action are so rapid, it may find a useful niche in the prehospital setting when used by emergency medical technicians and possibly by an occasional labile asthmatic patient at home."9

What is the Downside?

As mentioned, helium is inert, and heliox has no inherent adverse effects. However, its effect on gas density, and hence its potential physiologic effects, wane rapidly as FIO2 rises, and it is doubtful whether patients requiring much more than 30% oxygen could be expected to benefit. It would not be appropriate to allow a patient to remain hypoxemic in order to administer heliox. Hypoxemia is potentially life-threatening in acute asthma, and its correction is much more important than any potential gain from the use of heliox.

Heliox may adversely affect the function of respiratory care equipment such as flow meters, ventilators, nebulizers, and pulmonary function monitors.10,11 However, in my opinion, the most important potential "adverse effect" of heliox in patients with acute severe asthma would be if its use delayed or de-emphasized the most effective therapies for this condition—aerosolized bronchodilators and systemically administered corticosteroids.

What is the Bottom Line?

Heliox has become a recognized therapy in acute asthma, and it is within the scope of accepted practice to try it in patients whose asthma is severe and who do not respond to intensive initial interventions. Its use would seem to make the most sense in patients with very severe acute asthma of sudden onset, as these patients may represent a subset of asthmatics at increased risk of death.12,13 However, my opinion is that it is better to use proven therapies more aggressively than to add less established and more controversial interventions such as heliox—particularly if "the basics" have not been given using optimal technique, in sufficient doses, and for a long enough time.

As with other adjunctive therapies in acute respiratory failure (inhaled nitric oxide comes to mind), compelling physiologic rationale and anecdotal successes do not necessarily translate to clinically important benefits for patients on more rigorous examination using the scientific method. In acute severe asthma, prompt, aggressive therapy with aerosolized bronchodilators and systemic corticosteroids results in marked improvement over several hours in the vast majority of patients. Despite its safety and relatively modest cost, the evidence for a clinically important additional benefit of heliox in this setting is not convincing.

References

1. Barach AL. The use of helium in the treatment of asthma and obstructive lesions of the larynx and trachea. Ann Intern Med. 1935;9:739-765.

2. Manthous C, et al. Heliox in the treatment of airflow obstruction: A critical review of the literature. Respir Care. 1997;42:1034-1042.

3. Hess DR, et al. The effect of heliox on nebulizer function using a beta-agonist bronchodilator. Chest. 1999;115(1):184-189.

4. Kress JP, et al. The utility of albuterol nebulized with heliox during acute asthma exacerbations. Am J Respir Crit Care Med. 2002;165(9):1317-1321.

5. Rodrigo G, et al. Heliox for treatment of exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2002;(2):CD003571.

6. Rodrigo GJ, et al. Use of helium-oxygen mixtures in the treatment of acute asthma. Chest. 2003;123:891-896.

7. Ho AMH, et al. Heliox vs air-oxygen mixtures for the treatment of patients with acute asthma. Chest. 2003; 123:882-890.

8. Manthous CA. Heliox for status asthmaticus? Chest. 2003;123:676-677.

9. Kass JE. Heliox redux. Chest. 2003;123:673-676.

10. Chatmongkolchart S, et al. In vitro evaluation of aerosol bronchodilator delivery during noninvasive positive pressure ventilation: Effect of ventilator settings and nebulizer position. Crit Care Med. 2002; 30(11):2515-2519.

11. Chatmongkolchart S, et al. Heliox delivery with noninvasive positive pressure ventilation: A laboratory study. Respir Care. 2001;46(3):248-254.

12. Wasserfallen JB, et al. Sudden asphyxic asthma: A distinct entity? Am Rev Respir Dis. 1990;142(1):108-111.

13. Woodruff PG, et al. Sudden-onset severe acute asthma: Clinical features and response to therapy. Acad Emerg Med. 1998;5(7):695-701.

Dr. Pierson is Professor of Medicine University of Washington Medical Director Respiratory Care Harborview Medical Center Seattle.